Molecular reference controls

Abstract

Reference controls for use in downstream molecular technologies comprising a control composition including a sample base matrix, such as at least one biological fluid or biological fluid component, at least one condition component processed to be indicative of a condition, and at least one cross-linking agent.

1 . A control composition for indicating positive presence of a condition comprising:
 at least one biological fluid or biological fluid component;   at least one condition component processed to be indicative of a condition; and   at least one cross-linking agent.   
     
     
         2 . The control composition of  claim 1 , wherein the control composition includes an aldehyde and/or aldehyde donor agent. 
     
     
         3 . The control composition of claim of any of the preceding claims, wherein the at least one biological fluid is blood. 
     
     
         4 . The control composition of any of the preceding claims, wherein the at least one biological fluid is selected from the group consisting of blood, serum, plasma, urine, fecal matter, saliva, sputum, cerebral spinal fluid, vaginal secretions, and semen. 
     
     
         5 . The control composition of any of the preceding claims, wherein the at least one biological fluid is blood culture or bacterial culture. 
     
     
         6 . The control composition of any of the preceding claims, wherein the at least one biological fluid or biological fluid component is of human origin. 
     
     
         7 . The control composition of any of the preceding claims, wherein the at least one biological fluid or biological fluid component is of animal origin. 
     
     
         8 . The control composition of any of the preceding claims, wherein the at least one biological fluid component is selected from the group consisting of white blood cells, red blood cells, cell-free nucleic acids, proteins, fragmented nucleic acids, fragmented proteins, and any synthetic or engineered combination thereof. 
     
     
         9 . The control composition of any of the preceding claims, wherein the at least one biological fluid component is a nucleic acid or protein. 
     
     
         10 . The control composition of any of the preceding claims, wherein the at least one condition component indicative of a condition is selected from the group consisting of inactivated viruses, attenuated viruses, plasm ids, bacteria, fungi, parasites, microbiota, engineered cell lines, wild-type cells and/or any microbiome combination thereof. 
     
     
         11 . The control composition of any of the preceding claims, wherein the at least one biological fluid component is an endogenously and/or exogenously modified component to indicate one or more of mutation, glycosylation, methylation, acetylation, ubiquitination, S-Nitrosylation, lipidation, GPI anchors, myristoylation, palmitoylation, prenylation, and phosphorylation. 
     
     
         12 . The control composition of any of the preceding claims, wherein the at least one condition component is an inactivated pathogen. 
     
     
         13 . The control composition of any of the preceding claims, wherein the at least one condition component is an inactivated virus. 
     
     
         14 . The control composition of any of the preceding claims, wherein the at least one condition component is bacteria. 
     
     
         15 . The control composition of any of the preceding claims, wherein the at least one condition component is at least one Gram-negative organism that contains at least one mechanism of drug or treatment resistance. 
     
     
         16 . The control composition of any of the preceding claims, wherein the at least one condition component is at least one Gram-positive organism that contains at least one mechanism of drug or treatment resistance. 
     
     
         17 . The control composition of any of the preceding claims, wherein the at least one condition component includes an immortalized and/or primary cell line containing a mutant phenotype or other molecular signature of interest. 
     
     
         18 . The control composition of any of the preceding claims, wherein the control composition serves an external control. 
     
     
         19 . The control composition of any of the preceding claims, wherein the control composition serves as an internal control. 
     
     
         20 . The control composition of any of the preceding claims, wherein the control composition serves as an internal control and the at least one biological fluid component is a nucleic acid that is a control target of interest. 
     
     
         21 . The control composition of any of the preceding claims, wherein the at least one biological fluid component is treated to mimic effects of a condition. 
     
     
         22 . The control composition of any of the preceding claims, wherein the at least one biological fluid is substantially free of any treatment to mimic effects of a condition. 
     
     
         23 . The control composition of any of the preceding claims, wherein the control composition is substantially free of any time-dependent component degradation when stored at room temperature. 
     
     
         24 . The control composition of any of the preceding claims, wherein the control composition is substantially free of any time-dependent component degradation when stored at 4° C. 
     
     
         25 . The control composition of any of the preceding claims, wherein the control composition is substantially free of any time-dependent component degradation when stored at 37° C. 
     
     
         26 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes an aldehyde with one or more reactive groups. 
     
     
         27 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes formaldehyde, glutaraldehyde, phthaldehyde or a combination thereof. 
     
     
         28 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes N-Hydroxysuccinimide (NHS) ester functional group(s). 
     
     
         29 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes disuccinim idyl suberate and/or bis[sulfosuccinim idyl] suberate. 
     
     
         30 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes maleimide functional group(s). 
     
     
         31 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes dithiobismaleimidoethane (DTME) and/or bismaleimidohexane (BMH). 
     
     
         32 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent includes one or more functional groups of the following: haloacetyls, imidoesters, pyridyl disulfides, hydrazides, alkoxyamines, and carboiimides. 
     
     
         33 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent is homobifunctional. 
     
     
         34 . The control composition of any of the preceding claims, wherein the at least one cross-linking agent is heterobifunctional. 
     
     
         35 . The control composition of any of the preceding claims, wherein the control composition includes a formaldehyde donor agent including imidazolidinyl urea (IDU), diazolidinyl urea (DU) or a combination thereof. 
     
     
         36 . The control composition of any of the preceding claims, wherein the control composition includes chemical analytes and/or metabolites. 
     
     
         37 . The control composition of any of the preceding claims, wherein the control composition includes one or more surfactants. 
     
     
         38 . The control composition of any of the preceding claims, wherein the control composition includes one or more metabolic inhibitors. 
     
     
         39 . The control composition of any of the preceding claims, wherein the control composition includes one or more nuclease inhibitors. 
     
     
         40 . The control composition of any of the preceding claims, wherein the control composition includes one or more organic components. 
     
     
         41 . The control composition of any of the preceding claims, wherein the control composition is utilized for one or more of the following: nucleic acid/protein purification protocols, sample-to-answer testing platforms, polymerase chain reaction protocols, fluorescence in situ hybridization (FISH) testing, genetic sequencing, flow cytometry, enzymatic testing, mass spectrometry or enzyme-linked immunosorbent assay (ELISA) testing. 
     
     
         42 . The control composition of any of the preceding claims, wherein the control composition includes a stabilization period of about 15 minutes to about 120 hours. 
     
     
         43 . The control composition of any of the preceding claims, wherein the control composition includes a stabilization period of about 15 minutes. 
     
     
         44 . The control composition of any of the preceding claims, wherein the control composition is stable at room temperature. 
     
     
         45 . The control composition of any of the preceding claims, wherein the control composition is stable for at least up to 180 days at one or more of the following: 4° C., room temperature and 37° C.